The identification of human tumor antigens recognized by the autologous host is yielding new and promising target molecules for immunotherapy, diagnosis and monitoring of human cancer (1-4). Studies of the cellular and humoral immune response to cancer have revealed an extensive repertoire of tumor antigens recognized by the immune system, collectively termed the cancer immunome (5).
The immunome is composed largely of antigens defined by T-cell epitope cloning (1-3, 6, 7), MHC peptide elution (8-10), and serological expression cloning (SEREX, 4, 5, 11-14), and is catalogued in three databases: the peptide database of T-cell defined tumor antigens (authored by members of the Ludwig Institute for Cancer Research (LICR) that is available on the website of Cancer Immunity, Journal of the Academy of Cancer Immunology, cancerimmunity.org/peptidedatabase/Tcellepitopes); the SYFPEITHI database of MHC ligands and peptide motifs (available on the website of Biomedical Informatics-Heidelberg, bmi-heidelberg.com/syfpeithi/) and the SEREX database (available on the website of the LICR, licr.org/SEREX.html).
SEREX is a method of immunoscreening tumor-derived cDNA expression libraries with cancer patient sera in order to identify molecules recognized by high titered IgG antibodies (11) As archived in the SEREX database, approximately 1000 distinct antigens have been defined by SEREX analysis, including a number of etiologically and therapeutically significant cancer antigens, such as mutational antigens (e.g. p53, LKB1, BUB1; refs. 12-14), differentiation antigens (e.g. tyrosinase, NY-BR-1, rab 38; refs. 5, 11, 15), overexpressed gene products (e.g. Her2neu, TPD52, eIF4-gamma; refs. 14, 16) and cancer/testis antigens (e.g. MAGE-1, NY-ESO-1, SSX-2; refs. 4, 11).
Cancer/testis (CT) antigens represent a group of shared, tumor-specific antigens expressed exclusively in developing germ cells of the testis and fetal ovary, as well as in placental trophoblast, and most notably, in a proportion of human cancers of diverse origins (16). On the basis of tissue-restricted expression and immunogenicity, CT antigens are attractive targets for vaccine-based immunotherapies. In general, CT antigens are expressed in 20-40% of specimens from a given tumor type (17-19). One exception to this is synovial sarcoma, in which 80% of specimens express NY-ESO-1 (20) and MAGE antigens (21). Thus, identification of additional CT antigens and other genes having a tumor-associated expression profile is needed for the development of additional therapeutics and diagnostics to permit effective treatment and diagnosis of a broader group of cancer patients.